Anti-tumor efficacy of Cloretazine (VNP40101M) alone and in combination with fludarabine in murine tumor and human xenograft tumor models.

Abstract

Cloretazine (VNP40101M), a new sulfonylhydrazine alkylating agent, has demonstrated broad-spectrum anti-tumor activity in preclinical studies. In this study, Cloretazine was evaluated both as a monotherapy and in combination with fludarabine in murine tumor and human tumor xenograft models. Cloretazine significantly inhibited the growth of subcutaneously implanted tumors, including B16F10 murine melanoma in C57BL/6 mice, and H460 human lung carcinoma and WiDr human colon carcinoma in athymic nude CD1 mice. The inhibition of tumor growth by Cloretazine was dose dependent, increasing from 42.2 to 87% as the dose escalated from 100 to 150 mg/kg. Cloretazine showed equivalent efficacy but lower toxicity compared to cyclophosphamide in these models. The combination therapy, consisting of a single dose of 10 mg/kg Cloretazine plus five doses of 70 mg/kg fludarabine, given every other day intraperitoneally, significantly increased the long-term survival of BDF1 mice bearing the L1210 murine leukemia. On Day 65 post-tumor implantation, the combination therapy yielded a 90% survival rate compared to 40% for Cloretazine alone and 0% for fludarabine alone.

• Authors: Li-mou Zheng, Zujin Li, Lanzhen Liu, Bai Louis Song, Ivan King
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 60 Issue 1 Pg. 45-51 (Jun 2007) ISSN: 0344-5704 [Print] Germany
• PMID: 17256135 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• Hydrazines
• Sulfonamides
• laromustine
• Cyclophosphamide
• Vidarabine
• fludarabine

Topics

• Animals
• Antineoplastic Agents, Alkylating (administration & dosage, chemistry, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Line, Tumor
• Cyclophosphamide (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor (methods)
• Humans
• Hydrazines (administration & dosage, chemistry, therapeutic use)
• Injections, Intraperitoneal
• Leukemia L1210 (drug therapy, pathology)
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Sulfonamides (administration & dosage, chemistry, therapeutic use)
• Survival Analysis
• Time Factors
• Tumor Burden (drug effects)
• Vidarabine (administration & dosage, analogs & derivatives)
• Weight Loss
• Xenograft Model Antitumor Assays (methods)